Prostate CancerPhase 2NCT02346526
A Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer
A Phase 2 study testing Blood Tests, CT scan and FACBC PET/MRI in a subset of participants in people with Prostate Cancer and Castration-resistant Prostate Cancer, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this study is to look for markers of how Ra-223 improves the lives of men with prostate cancer. This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Castration-resistant Prostate Cancer, Castration-resistant Prostate Cancer Metastatic to Bone
- What is being tested?
- Blood Tests, CT scan and FACBC PET/MRI in a subset of participants
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male age ≥ 18 years.
- Histologically or cytologically confirmed adenocarcinoma of the prostate. Life expectancy of at least 6 months.
- ECOG performance status of zero, one, or two.
- Bone-predominant metastatic CRPC: at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed).
- Symptomatic as defined by either of the following:
- (a) Regular use of analgesic medication for cancer-related bone pain (≥ level 1; WHO ladder for cancer pain), or
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- (b) Treatment with EBRT for bone pain (though EBRT must be completed ≥12 weeks prior to enrollment in this trial).
- Judged by investigator to have progressive disease sufficient to clinically justify standard-of-care radium-223 treatment.
- Subjects must be able to understand and be willing to sign the written informed consent form.
- All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).
- No intention to use cytotoxic chemotherapy within the next 6 months. Subjects must agree to use adequate contraception beginning at the signing of the ICF until at least 6 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator.
- Acceptable hematology and serum biochemistry screening values:
- White Blood Cell Count (WBC) ≥ 3,000/mm3
- Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
- Platelet (PLT) count ≥ 100,000/mm3
- Hemoglobin (HGB) ≥10 g/dl (Please note: it is acceptable from the standpoint of study eligibility to undergo transfusion in order to achieve hemoglobin ≥ 10 g/dl)
- Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
- Creatinine ≤ 1.5 x ULN
- Albumin > 25 g/L
- Willing and able to comply with the protocol, including follow-up visits and examinations.
Who cannot join
- Treatment with cytotoxic chemotherapy within previous 28 days, or failure to recover from AEs due to cytotoxic chemotherapy administered more than 28 days previous (however, ongoing neuropathy is permitted).
- Received any investigational compound within 28 days prior to the first dose of study drug or planned during the treatment period or follow-up.
- Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases.
- Received previous radiotherapy to approximately >25% of bone marrow.
- Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer).
- Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) or other imaging modality.
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- Presence of brain metastases.
- Lymphadenopathy exceeding 6 cm in short-axis diameter.
- Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.
- Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.
- Any other serious illness or medical condition, such as but not limited to:
- Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2
- Cardiac failure New York Heart Association (NYHA) III or IV
- Crohn's disease or ulcerative colitis
- Known bone marrow dysplasia
- Fecal incontinence.
- Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Single-arm Open Label Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer
The purpose of this study is to look for markers of how Ra-223 improves the lives of men with prostate cancer. This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
This research study is designed to examine a treatment strategy that is standard but still relatively new. Ra-223 consists of a series of six infusions given once every 4 weeks. It was FDA approved in 2013 for the treatment of prostate cancer that has spread to bone and has grown despite ADT ("hormonal therapy").
Ra-223 was approved because it was shown to improve the length of the lives of the men with prostate cancer who received it. Despite that important benefit, it is not known to improve other standard markers of prostate cancer such as PSA blood tests (a blood marker that is used to track cancer activity in men who have prostate cancer) and standard imaging scans such as bone scans and computed tomography (CT) scans. If participants and their doctors do not have good markers of whether or not the cancer is responding to therapy, it is harder to make decisions about whether to continue that therapy. This is a current problem.
This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.
- Conditions
- Prostate Cancer, Castration-resistant Prostate Cancer, Castration-resistant Prostate Cancer Metastatic to Bone
- Being tested
- Blood Tests, CT scan, FACBC PET/MRI in a subset of participants, Radium-223 dichloride, bone scan
- Keywords
- Prostate Cancer, Castration-resistant prostate cancer, Castration-resistant prostate cancer metastatic to bone
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood TestsProcedure or surgery
Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93.
CT scanProcedure or surgery
Standard CT scans will be carried out prior to treatment, week 9, and week 25.
FACBC PET/MRI in a subset of participantsProcedure or surgery
Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9.
Radium-223 dichlorideDrug
Also called Xofigo
Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments.
bone scanProcedure or surgery
Standard bone scans will be carried out prior to treatment, week 9, and week 25.
| Study group | Role | What they receive |
|---|---|---|
| Radium-223 dichloride | Experimental | After the screening procedures confirm that a patient is eligible to participate in the research study.
Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring.
* Blood Tests
* CT scan
* Bone scan
* FACBC PET/MRI in a subset of participants Receives: Procedure: Blood Tests; Procedure: CT scan; Procedure: FACBC PET/MRI in a subset of participants; Drug: Radium-223 dichloride; Procedure: bone scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Scan Index
Automated bone scan index (aBSI) is an imaging prognostic biomarker used to quantitatively assess effect of therapy. aBSI expresses the tumor burden in bone as a percent of the total skeletal mass. An aBSI value of 1.0 indicates the tumor(s) to be present in 1% of the entire skeleton (arms and legs included).
Measured: Baseline to 2 Months
Secondary outcomes (5)
Percentage of Skeletal Mass Occupied by a Lesion, Stratified by 18 Month Survival Status
Mean change in automated bone scan index (aBSI) at 2 months (i.e. approximately week 9) as assessed by aBSI will be described by 18 month survival status. In other words, decline in aBSI at 2 months on therapy will be evaluated as a predictive biomarker of survival at 18 months.
Measured: Baseline and 2 months
Circulating Tumor Cell (CTC) Number
The presence of circulating tumor cells (CTCs) in the peripheral blood, will be assessed by by the FDA-approved assay CELLSEARCH® CTC Test, is associated with decreased progression-free survival and decreased overall survival in patients treated for metastatic prostate cancer.
Measured: Baseline/Day 1, Day 30, Day 60
Circulating Biomarkers of the Tumor Microenvironment
Bone turnover markers (i.e., serum bone specific alkaline phosphatase and N-telopeptide) and plasma biomarkers of inflammation and angiogenesis will be assessed serially. Our analyses of circulating biomarkers of the tumor microenvironment were more limited than originally planned due to a freezer malfunction that compromised our frozen samples that had been saved for later batched analyses. The reported values within the table below reflect CTCm score which is a previously described analysis that uses droplet digital PCR to assess gene expression from circulating tumor cells (CTCs) isolated using the microfluidic CTC-iChip. CTCm score, by published convention, does not have units and does not have a normal range.
In the present study, the normalized CTCm score was calculated as described previously using weighting coefficients. It is considered better to have a lower CTCm score. The table contains [mean (standard deviation)] of CTCm score for each group at the specified timepo
Measured: Baseline/Day 1, Day 30, Day 60
Baseline Pain Score Evaluation as a Predictor of Survival
Pain and narcotic analgesic use was assessed by the 4-item Brief Pain Inventory (BPI). This instrument contains 4 items, with each item reported on a scale of 0-10, meaning that total possible range is 0-40. For each question's 0-10 response scale, 0 meant no pain/interference and 10 meant worst pain imaginable/complete interference.
Overall survival (OS) was defined as the interval between the start of therapy and the date of death or censor. For the analysis presented in the table, the algorithm of Contal-O'Quigley was applied to the data using leave-one-out jack-knife resampling to determine the optimal division points according to pain score on 4-item BPI at baseline. Each iteration of the algorithm produced an estimate of the "best" division point based on the data. With this method, optimal cut-point for this cohort was baseline total BPI score < 8 vs ≥8. Median survival for each sub-group is reported as months (with range in parentheses).
Measured: Baseline through study completion, up to approximately 5 years
Baseline Global Health Score Evaluation as a Predictor of Survival
Baseline Global Health Score was reported by participants on a scale of 0 ("The worst health you can imagine") to 100 ("The best health you can imagine"). Overall survival (OS) was defined as the interval between the start of therapy and the date of death or censor, expressed here in months.
For the analysis presented in the table, the algorithm of Contal-O'Quigley was applied to the data using leave-one-out jack- knife resampling to determine the optimal division points according to Global Health Score at baseline. Each iteration of the algorithm produced an estimate of the "best" division point based on the data. With this method, optimal cut-point for this cohort was baseline Global Health Score ≥95 or <95. Median survival for each sub-group is reported as months (with range in parentheses).
Measured: Baseline through study completion, up to approximately 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2015 (estimated)
- Study startApr 2015
- Primary completionOct 2019
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Philip J. Saylor, MD, Massachusetts General Hospital
- Investigators
- Philip J Saylor, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02346526
- Sponsor's protocol ID
- 14-375
- Other IDs
- ONC-2013-119
- Status last verified
- Sep 2022
- First submitted
- 13 Jan 2015
- Last updated
- 29 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm Open Label Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02346526
- Acronym / sponsor ID
- 14-375
- Conditions
- Prostate Cancer, Castration-resistant Prostate Cancer, Castration-resistant Prostate Cancer Metastatic to Bone
- Keywords
- Prostate Cancer, Castration-resistant prostate cancer, Castration-resistant prostate cancer metastatic to bone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Apr 2015 (actual)
- Primary completion
- Oct 2019 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 27 Jan 2015 (estimated)
- Results
- Posted 29 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to look for markers of how Ra-223 improves the lives of men with prostate cancer. This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
This research study is designed to examine a treatment strategy that is standard but still relatively new. Ra-223 consists of a series of six infusions given once every 4 weeks. It was FDA approved in 2013 for the treatment of prostate cancer that has spread to bone and has grown despite ADT ("hormonal therapy").
Ra-223 was approved because it was shown to improve the length of the lives of the men with prostate cancer who received it. Despite that important benefit, it is not known to improve other standard markers of prostate cancer such as PSA blood tests (a blood marker that is used to track cancer activity in men who have prostate cancer) and standard imaging scans such as bone scans and computed tomography (CT) scans. If participants and their doctors do not have good markers of whether or not the cancer is responding to therapy, it is harder to make decisions about whether to continue that therapy. This is a current problem.
This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radium-223 dichloride | Experimental | Procedure: Blood Tests, Procedure: CT scan, Procedure: FACBC PET/MRI in a subset of participants, Drug: Radium-223 dichloride, Procedure: bone scanAfter the screening procedures confirm that a patient is eligible to participate in the research study. Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring. * Blood Tests * CT scan * Bone scan * FACBC PET/MRI in a subset of participants |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Male age ≥ 18 years.
- Histologically or cytologically confirmed adenocarcinoma of the prostate. Life expectancy of at least 6 months.
- ECOG performance status of zero, one, or two.
- Bone-predominant metastatic CRPC: at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed).
- Symptomatic as defined by either of the following:
Key exclusion criteria (17 listed)
- Treatment with cytotoxic chemotherapy within previous 28 days, or failure to recover from AEs due to cytotoxic chemotherapy administered more than 28 days previous (however, ongoing neuropathy is permitted).
- Received any investigational compound within 28 days prior to the first dose of study drug or planned during the treatment period or follow-up.
- Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases.
- Received previous radiotherapy to approximately >25% of bone marrow.
- Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood TestsBlood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93. | Procedure or surgery | Radium-223 dichloride |
| CT scanStandard CT scans will be carried out prior to treatment, week 9, and week 25. | Procedure or surgery | Radium-223 dichloride |
| FACBC PET/MRI in a subset of participantsApproximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9. | Procedure or surgery | Radium-223 dichloride |
| Radium-223 dichlorideAlso: XofigoRa-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. | Drug | Radium-223 dichloride |
| bone scanStandard bone scans will be carried out prior to treatment, week 9, and week 25. | Procedure or surgery | Radium-223 dichloride |
Primary outcome
Bone Scan Index
Time frame: Baseline to 2 Months
Automated bone scan index (aBSI) is an imaging prognostic biomarker used to quantitatively assess effect of therapy. aBSI expresses the tumor burden in bone as a percent of the total skeletal mass. An aBSI value of 1.0 indicates the tumor(s) to be present in 1% of the entire skeleton (arms and legs included).
5 secondary outcomes
Percentage of Skeletal Mass Occupied by a Lesion, Stratified by 18 Month Survival Status
Time frame: Baseline and 2 months
Circulating Tumor Cell (CTC) Number
Time frame: Baseline/Day 1, Day 30, Day 60
Circulating Biomarkers of the Tumor Microenvironment
Time frame: Baseline/Day 1, Day 30, Day 60
Baseline Pain Score Evaluation as a Predictor of Survival
Time frame: Baseline through study completion, up to approximately 5 years
Baseline Global Health Score Evaluation as a Predictor of Survival
Time frame: Baseline through study completion, up to approximately 5 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip J Saylor, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Blood Tests, CT scan and FACBC PET/MRI in a subset of participants in people with Prostate Cancer and Castration-resistant Prostate Cancer, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone Scan Index (time frame: Baseline to 2 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022; AzTrials last refreshed its copy on 8 Nov 2026.